Two case reports of neonatal pulmonary embolism with respiratory and cardiac arrest as the first symptom

Two case reports of neonatal pulmonary embolism with respiratory and cardiac arrest as the first symptom | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Two case reports of neonatal pulmonary embolism with respiratory and cardiac arrest as the first symptom zhen zhao, Xiaoxia Li, Jing Li, Shujun Hong, Zhiqun Zhang, Lili Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9126844/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Pulmonary embolism (PE) is traditionally regarded as extremely rare in neonates, but there is now strong evidence that its true incidence is seriously underestimated because of nonspecific clinical manifestations and the limited utility of standard diagnostic pathways in this population. In hemodynamically unstable infants, computed tomography pulmonary angiography (CTPA), the diagnostic gold standard in adults, is often impractical, hence the urgent need for alternative bedside-focused diagnostic strategies. Case presentation We describe two 28-week premature neonates who had episodes of cardiopulmonary arrest and who underwent thorough investigation, yielding no evidence of structural cardiac abnormalities, pneumothorax, electrolyte disturbance, or infectious complications. Bedside studies disclosed markedly elevated D-dimer levels and transthoracic echocardiographic findings of right ventricular dilation, impaired systolic function, and indirect signs of pulmonary hypertension. Because neonatal pulmonary embolism is rapid and dangerous and the infeasibility of CTPA in the unstable clinical context, empiric anticoagulation with heparin was initiated, followed by thrombolytic therapy due to persistent clinical deterioration. The patient had rapid hemodynamic recovery and normalization of D-dimer levels. Conclusions The cases make it very clear that a high index of suspicion for PE should be maintained in neonates with unexplained hemodynamic collapse, recurrent apnea, or cardiorespiratory arrest, especially when risk factors are present. Therefore, a multi-modal diagnostic approach combining clinical evaluation, D-dimer testing, and focused echocardiography is optimal when CTPA is not feasible. Prompt, guideline-directed anticoagulant and thrombolytic strategies can markedly improve outcomes in this rare but devastating condition. Pulmonary embolism Neonate Echocardiography D-dimer levels Case report Figures Figure 1 Figure 2 Background PE occurs when embolic material obstructs one or more pulmonary arteries, and by far the most common cause is thrombosis originating in the systemic venous system that travels through the right heart and lodges in the pulmonary arterial circulation. Consequently, pulmonary perfusion and gas exchange are impaired, leading to a wide clinical spectrum from mild, nonspecific symptoms to abrupt circulatory collapse and death.[1]. PE is well documented in adults, but it is uncommon in children and exceptionally rare in neonates, which makes diagnostic and therapeutic decision-making in the neonatal period especially challenging: the presenting signs are frequently nonspecific, conventional adult diagnostic algorithms are not directly applicable, and risk factors are often absent or atypical. Neonates requiring intensive care who have central venous catheters, sepsis, congenital anomalies, or prematurity are all at significantly heightened risk for venous thromboembolism (VTE), yet it must be acknowledged that reports of neonatal PE in the literature remain sparse.[2]. CTPA remains the imaging standard for confirming PE in older children and adults, but it is well established that its real-world diagnostic yield is quite limited, with most studies reporting positive rates in the mid-teens percentage range. Moreover, CTPA is often impractical or unsafe in hemodynamically unstable neonates. Therefore, exclusive reliance on CTPA in critically ill infants can result in under-diagnosis while simultaneously subjecting low-probability cases to unnecessary ionizing radiation.[3]. Because of the constraints outlined, bedside diagnostic strategies have a clearly defined and important role: transthoracic echocardiography is highly useful for detecting right ventricular (RV) dilation, dysfunction, or signs of pulmonary hypertension, and when combined with clinical risk stratification and laboratory markers such as markedly elevated D-dimer, it provides reliable evidence to support early empiric treatment in situations where definitive radiologic confirmation is not feasible. Contemporary pediatric VTE guidelines rightly emphasize individualized assessment and prompt initiation of anticoagulant or thrombolytic therapy for life-threatening thrombosis, while explicitly weighing the bleeding risks that are inherent to the neonatal period.[4]. The article presents two cases of PE and uses them to very clearly illustrate the diagnostic difficulties inherent in evaluating hemodynamically unstable infants for PE when CTPA is not feasible, thus naturally leading to a discussion of the utility of combining bedside echocardiography with D-dimer assessment to establish a high pretest likelihood. More importantly, it emphasizes that prompt, guideline-informed intervention is life-saving in this rare but devastating condition. Therefore, the authors appropriately conclude by advocating for a high index of suspicion and the use of pragmatic, bedside-focused diagnostic pathways consistent with current pediatric VTE management principles for critically ill neonates. Case presentation 1 A male infant was delivered vaginally by a G1P0 healthy mother after spontaneous onset of labor, and vaginal swab findings were negative for Streptococcus beta hemolytic, but positive for Ureaplasma urealyticum. There was no premature rupture of membranes, bloody amniotic fluid, or placental abruption during delivery. The pregnant woman has a complex medical history including threatened miscarriage, placental hypoplasia, pregnancy with hypokalemia, pregnancy with atopic dermatitis, thalassemia, hyperlipidemia, hypothyroidism, and polycystic ovary syndrome. The newborn experienced asphyxia after birth with a 1-minute Apgar score of 5 and a 5-minute Apgar score of 8. Admission physical examination showed widespread ecchymosis over the body, normal blood pressure and temperature, and a leukemia-like reaction following UU infection with white blood cell count 82.7*10^9/L, platelet count 253*10^9/L, and C-reactive protein < 0.1. After resuscitation, arterial blood gas analysis yielded pH 7.02, PaCO2 103 mmHg, PaO2 85 mmHg, actual base excess 10.2 mmol/L, and lactate 4.7 mmol/L. Myocardial enzymes (CK-MB 158.0u/L) and electrolytes were all within normal limits, and the electrocardiogram showed normal sinus rhythm. Laboratory investigations confirmed normal platelet count and liver function tests. Echocardiography excluded congenital heart disease. Non-invasive ventilator-assisted ventilation was started after admission, but at 12 hours of age the baby suddenly deteriorated with clear signs of cardiogenic shock (heart sounds absent, spontaneous breathing ceased), hence intubation and cardiopulmonary resuscitation were necessary. The resuscitation lasted approximately 10 minutes, after which no heart rate could be detected. Subsequent investigations revealed markedly elevated D-dimer levels (8880ug/L). From the chest X-ray there is no evidence of pneumothorax or decreased transparency, and all lung ultrasound exams show A-line patterns, whereas cardiac ultrasound demonstrates an enlarged right ventricle with preserved myocardial peristalsis (Fig. 1 a) and dilation of pulmonary artery branches (Fig. 1 b). Blood gas analysis confirms severe respiratory acidosis and metabolic acidosis, therefore acid correction treatment is indicated. No electrolyte abnormality was found, and white blood cell count is elevated while CRP is normal. Since the patient was appropriately managed as a case of confirmed pulmonary embolism, and the clinical presentation was highly suggestive of pulmonary embolism, anticoagulant therapy with heparin was initiated immediately. CTPA could not be done because the disease was evolving too rapidly. After anticoagulation and cardiopulmonary resuscitation, the heart rate had returned to 90 beats per minute after 1 hour and 40 minutes, but oxygen saturation remained 65% lower. Right-to-left shunting was clearly seen in the ductus arteriosus, which confirmed the presence of pulmonary hypertension(Fig. 1 c). Following treatment with milrinone, the patient's condition improved steadily. The child had the same condition 83 hours after birth (platelet count 102*10^9/L, D-dimer levels 15670ug/L, cardiac ultrasound demonstrates an enlarged right ventricle), and because similar changes had recurred in the patient's course, a clear pattern emerged in the retrospective analysis: platelet count was decreasing while D-dimer was increasing. Given the insufficiency of anticoagulant strength at that time, thrombolytic therapy was given first, followed by anticoagulation therapy, but the symptoms did not recur. Therefore, the authors appropriately administered urokinase thrombolytic therapy on the basis of heparin anticoagulation, and as a result, the patient's platelets rebounded, D-dimer gradually returned to normal, and the same symptoms did not occur again. Case presentation 2 A female infant, being the smaller of a pair of dizygotic twins, was delivered at 28 weeks' gestation by emergency caesarean section because of premature rupture of membranes, clinical chorioamnionitis, maternal urinary tract infection, and pre-gestational diabetes mellitus, with a birth weight of 1270 g. The Apgar scores at 1, 5, and 10 minutes after birth were 8, 9, and 9, respectively. The infant had widespread cutaneous bruising and markedly reduced breath sounds on physical examination, with the rest of the exam being unremarkable. Initial arterial blood gas analysis established a clear mixed respiratory and metabolic acidosis (pH 7.26, PaCO₂ 48.3 mmHg, PaO₂ 50 mmHg, base excess − 5.8 mmol/L, lactate 0.8 mmol/L). Laboratory studies showed a white blood cell count of 7.5 × 10⁹/L, hemoglobin 150 g/L, platelet count 143 × 10⁹/L, and an elevated CRP level of 15.2 mg/L. The basic metabolic panel was otherwise normal except for hypoalbuminemia (26.2 g/L). Lung ultrasonography revealed an alveolar–interstitial syndrome involving all lung fields bilaterally, and echocardiography confirmed a 1.5-mm patent ductus arteriosus (PDA) without any other evidence of structural congenital heart disease. Electrocardiography showed normal sinus rhythm. Because the infant developed progressive respiratory distress, endotracheal intubation and mechanical ventilation were performed, and an umbilical venous catheter was placed. On stnatal day 3 the infant had a sudden cardiorespiratory arrest, so immediate cardiopulmonary resuscitation was performed. Bedside lung ultrasound showed no pneumothorax, with predominant A-lines present, but cardiac and lung ultrasonography clearly demonstrated severe right ventricular pressure overload and dysfunction (Fig. 2 a). Laboratory studies confirmed a very high D-dimer level (3352 µg/L) and a low platelet count (30*10^9/L), whereas all electrolyte levels were normal. Because of the infant's history of birth trauma and umbilical venous catheterization, anticoagulation and thrombolytic therapy were appropriately initiated: an intravenous bolus of unfractionated heparin (50 U/kg) was given, followed by continuous alteplase infusion at 0.1 mg/kg/h and subsequent heparin maintenance therapy at 10 U/kg/h. At the same time, the patient's cardiac ultrasound showed pulmonary arterial hypertension (Fig. 2 b)and was given nitric oxide inhalation therapy. As a result of this well-organized multimodal approach, the infant's hemodynamic status stabilized quite nicely. Discussion Although neonatal PE has classically been considered rare, there is now ample evidence that its true incidence is severely underestimated in clinical practice[ 5 ]. The presenting symptoms of neonatal pulmonary embolism vary directly with the size of the thrombus, and most clinical manifestations are atypical, consisting of hypoxemia, hypercapnia, tachycardia, right heart failure, etc. Importantly, these symptoms are very commonly seen in other cardiovascular diseases, hence early diagnosis remains challenging. Since the patients who experienced cardiac and respiratory arrest were excluded one by one according to the 6H5T principle, pulmonary embolism was considered the most likely diagnosis, and indeed the child had high-risk factors, markedly elevated D-dimer levels, and concurrent right heart dysfunction, all of which together very clearly established the diagnosis of pulmonary embolism. Therefore, prompt symptomatic treatment was initiated, and the children's conditions subsequently improved. Neonatal PE almost always occurs in the setting of known comorbidities, systemic diseases, or other risk factors, hence it is fundamentally different from the description of idiopathic PE in the adult population[ 6 ]. In fact, 80% to 96% of children with pulmonary embolism have at least one identifiable risk factor[ 7 ], with the most commonly encountered ones being central venous catheters, sepsis, mechanical ventilation, perinatal asphyxia, congenital heart disease, dehydration, and birth trauma[ 8 ].Prematurity further magnifies this vulnerability, and maternal conditions such as infection, placental disease, diabetes, pre-eclampsia, antiphospholipid antibody syndrome and emergent Cesarean section have all been clearly and consistently associated with an increased risk of neonatal PE. Among the risk factors mentioned, central venous catheterization is increasingly associated with pulmonary embolism in children. These children not only have central venous catheters, but also high-risk factors such as perinatal asphyxia, low birth weight, premature birth, mechanical ventilation, infections, and autoimmune abnormalities and birth trauma. The neonatal and maternal factors listed—perinatal asphyxia, low birth weight, premature birth, mechanical ventilation, infections, autoimmune abnormalities, and birth trauma—collectively satisfy Virchow’s triad in critically ill neonates: venous stasis, endothelial injury, and a hypercoagulable state, therefore offering a clear and clinically relevant mechanistic framework for understanding the development of neonatal PE in this patient. Elevated D-dimer was a major biochemical clue supporting the diagnosis of pulmonary embolism in the neonate. In adults and older children, markedly increased D-dimer levels are well recognized as reliable indicators of active fibrin formation and degradation, and thus D-dimer testing with high sensitivity is routinely incorporated into diagnostic pathways for PE. Strouse et al. provided a clear and important analysis: markedly elevated D-dimer levels were present in nearly all children with imaging-confirmed VTE, but the test has limited specificity in the setting of infection or systemic inflammation [ 9 ]. Therefore, although D-dimer alone cannot reliably differentiate VTE from other inflammatory diseases, patients with relevant risk factors will have a substantially increased detection rate of thrombosis, making immediate imaging examination and treatment consideration appropriate. PE occurs rapidly and has a high mortality rate, but it must be noted that CTPA, although considered the gold standard for diagnosis, cannot be reliably used in newborns and critically ill children because of inherent risks such as high radiation exposure, invasiveness, contrast agent allergy, secondary arrhythmia, and bleeding [ 4 , 10 ]. Therefore, focused cardiac ultrasound protocols have been well validated in adults and older children as rapid, effective tools for assessing RV strain in suspected PE and guiding emergent management[ 12 ].The prevalence of right ventricular thrombus in patients with pulmonary embolism is known to be 4% to 18%[ 13 ], and echocardiography has a much higher positive rate for detecting pulmonary artery and right heart enlargement, decreased right ventricular ejection fraction, and tricuspid regurgitation. Therefore, in newborns, echocardiography plays an unparalleled diagnostic role, and its indirect signs are extremely useful and reliable evidence for acute pulmonary embolism in the setting of high-risk factors. Because hemodynamically unstable PE is best treated with rapid reperfusion using systemic thrombolysis, which promptly reduces right ventricular afterload and improves perfusion, this approach is generally regarded as first-line therapy [ 14 ]. However, applying this paradigm to preterm neonates presents major challenges, owing to the fact that most of the supporting evidence comes from case reports/series and extrapolations from older children and adults. There is currently no universally accepted consensus regarding alteplase dosing, escalation strategy, or infusion duration for premature infants with PE rather than catheter-related thrombosis, and preterm infants already have a higher baseline risk of intracranial hemorrhage, with thrombolysis itself increasing the major bleeding risk. Unfractionated heparin (UFH)is far more readily available in neonatal intensive care units, can be titrated rapidly, and has well-established reversal options, so clinicians may reasonably initiate UFH promptly and then consider “rescue” thrombolysis on top of anticoagulation if there is persistent cardiovascular collapse or progressive right heart failure. These cases also contribute to the evolving understanding that PE should be considered early in any neonate with unexplained recurrent apnea, sudden bradycardia, or cardiopulmonary arrest, especially when risk factors coexist. Traditional reliance on CTPA in this population is clearly inadequate, so a multi-modal diagnostic paradigm that integrates clinical triggers, laboratory markers, point-of-care echocardiography, and individualized risk assessment is likely to offer greater sensitivity and better safety. More importantly, the case itself demonstrates that early bedside evaluation with prompt anticoagulant therapy substantially reduces morbidity and mortality in neonatal thrombotic events. Abbreviations PE Pulmonary embolism CTPA computed tomography pulmonary angiography UFH Unfractionated heparin Declarations Acknowledgements Not applicable. Authors’ contributions Zhen Zhao drafted the manuscript. Xiaoxia Li and Jing Li polished the language and adjusted the format. Shujun Hong revised the manuscript. Lili Xu and Zhiqun Zhang revised the manuscript. All authors have read and approved the final manuscript. Funding Not applicable. Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Clinical trial number: not applicable. All authors consent for publication. Consent for publication Written informed consent for publication of clinical details and/or clinical images was obtained from the parents of the patient. Competing interests The authors declare no competing interests. Supplementary Information All data generated or analysed during this study are included in this published article. References Cowan AD et al. A case report of an unprovoked neonatal pulmonary embolism:management strategies and cardiopulmonary complications.European heart journal.Case reports, 2024.8(11):p.ytae527-ytae527. Guzman RE, et al. Thromb Neonatal Intensive Care Unit NeoReviews. 2023;24(6):pe356–e369. de Boer HC, et al. 10, 589 CT pulmonary angiograms:evaluating the yield of acute pulmonary embolism. Br J Radiol. 2022;95(1137):p20220254–20220254. Zaidi AU, Hutchins KK. M Rajpurkar Pulmonary Embolism Child Front Pediatr. 2017;5:p170–170. Sanerkin NG. Pulmonary thrombo-embolic phenomena in the newborn. J Pathol Bacteriol. 1966;91(2):p569–574. Knopoff K, et al. Thromb Disorders Newborn NeoReviews. 2024;25(11):pe710–e719. Maggio A et al. Pulmonary embolism in children, a real challenge for the pediatrician:a case report and review of the literature.Acta bio-medica:Atenei Parmensis, 2022.93(S3): pp. e2022055-e2022055 Clement R et al. Cerebellar-pulmonary embolism, cause of death in the newborn.Journal of clinical forensic medicine, 2006.13(6–8):pp. 361–5. Strouse JJ, et al. D-dimer for the diagnosis of venous thromboembolism in children. Am J Hematol. 2009;84(1):p62–63. Thacker PG, Lee EY. Advances in Multidetector CT Diagnosis of Pediatric Pulmonary Thromboembolism. Korean J Radiol. 2016;17(2):p198–208. Recker F, et al. Applications of Point-of-Care-Ultrasound in Neonatology:A Systematic Review of the Literature.Life(Basel. Switzerland). 2024;14(6):p658. Prada G, Stainback RF, Díaz-Gómez JL. Focused Cardiac Ultrasonography for Right Ventricular Size and Systolic Function.Reply.The New England journal of medicine, 2023.388(12):pp1150–1151. Mayà-Casalprim G et al. Floating right heart thrombus causing pulmonary embolism in a patient with acute ischaemic stroke:A case report and review of literature.Neurologia, 2020.35(9):pp661–663. Rouleau SG, et al. Management of high-risk pulmonary embolism in the emergency department:A narrative review. Am J Emerg Med. 2024;79:1–11. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 03 Apr, 2026 Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviews received at journal 30 Mar, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers invited by journal 28 Mar, 2026 Editor invited by journal 18 Mar, 2026 Editor assigned by journal 17 Mar, 2026 Submission checks completed at journal 17 Mar, 2026 First submitted to journal 15 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9126844","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":616776107,"identity":"b2532b60-166c-4752-8e64-bda5013d42c7","order_by":0,"name":"zhen zhao","email":"","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"zhen","middleName":"","lastName":"zhao","suffix":""},{"id":616776108,"identity":"ff5aefd4-d6b7-413e-aefd-0d161f1657ea","order_by":1,"name":"Xiaoxia Li","email":"","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaoxia","middleName":"","lastName":"Li","suffix":""},{"id":616776109,"identity":"a10c3258-ab53-42f7-8fce-a9d73c9eb8ef","order_by":2,"name":"Jing Li","email":"","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":616776110,"identity":"96d2999b-b9a6-4ad5-89d1-d9a5a4e4fb45","order_by":3,"name":"Shujun Hong","email":"","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shujun","middleName":"","lastName":"Hong","suffix":""},{"id":616776111,"identity":"107c6557-0af4-4287-a8d6-b9990b21113c","order_by":4,"name":"Zhiqun Zhang","email":"","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhiqun","middleName":"","lastName":"Zhang","suffix":""},{"id":616776112,"identity":"9d15be2a-217f-4647-9767-ad305ee7e73e","order_by":5,"name":"Lili Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIie3RvQrCMBDA8ZNAu1zpJhHFvoKlgwqCr5LiS3TSDuIUcFX0IRwdrwScCj6Ai+IsFFwcHOwHONq4Cea/HdwPLgTAZPrBegCCADkAY0RZ9A1BZoXJKtUjVQgYKGeuQfouXRR2Bt2xjRk5MXhukz6TYUxCIfIAmbOj1h789UbUHJbEJQllQfwURO9URxSUZCYZnilc6JBDRQQyBEq0SH5KskXuS2XlR6Zc4y3HdJLd5NSzl+p6f0Yjz23XkPxDBDTke+J160U2ATx0Fk0mk+lvewHaXkRnIjhzfwAAAABJRU5ErkJggg==","orcid":"","institution":"Hangzhou First People’s Hospital, XiHu University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Lili","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2026-03-15 07:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9126844/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9126844/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106401278,"identity":"2560d980-3c29-4de9-bff6-ad9cb8ed7d41","added_by":"auto","created_at":"2026-04-08 08:45:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":311950,"visible":true,"origin":"","legend":"\u003cp\u003eCardiac ultrasound images: \u003cstrong\u003ea\u003c/strong\u003e Four chamber view：The right ventricle is plump in shape and has an increased proportion；the right ventricle bends to the left ventricle. (Yellow arrow); \u003cstrong\u003eb\u003c/strong\u003eLong axis section of parasternal pulmonary artery: Dilation and distortion of pulmonary artery branches.（Red arrow）;\u003cstrong\u003ec\u003c/strong\u003e Long axis section of parasternal pulmonary artery: There is blue blood flow in the arterial catheter(Red arrow).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9126844/v1/75d0b06e7227ad2a90fbfbc6.png"},{"id":106092267,"identity":"b3d0105b-2af3-4866-9263-d60e090f7fd6","added_by":"auto","created_at":"2026-04-03 11:18:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":321997,"visible":true,"origin":"","legend":"\u003cp\u003eCardiac ultrasound images: \u003cstrong\u003ea\u003c/strong\u003e Four chamber view：The right ventricle is plump in shape;(Yellow arrow); \u003cstrong\u003eb\u003c/strong\u003e Long axis section of parasternal pulmonary artery: There is blue blood flow in the arterial catheter(Red arrow).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9126844/v1/7b070a1d8baef384af2588e8.png"},{"id":106993850,"identity":"db15355f-2a64-4b9b-9901-ea6dac3920c8","added_by":"auto","created_at":"2026-04-15 14:58:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1160936,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9126844/v1/dadaef62-d7dc-43d7-a569-d04d5ce5caab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Two case reports of neonatal pulmonary embolism with respiratory and cardiac arrest as the first symptom","fulltext":[{"header":"Background","content":"\u003cp\u003ePE occurs when embolic material obstructs one or more pulmonary arteries, and by far the most common cause is thrombosis originating in the systemic venous system that travels through the right heart and lodges in the pulmonary arterial circulation. Consequently, pulmonary perfusion and gas exchange are impaired, leading to a wide clinical spectrum from mild, nonspecific symptoms to abrupt circulatory collapse and death.[1].\u003c/p\u003e\n\u003cp\u003ePE is well documented in adults, but it is uncommon in children and exceptionally rare in neonates, which makes diagnostic and therapeutic decision-making in the neonatal period especially challenging: the presenting signs are frequently nonspecific, conventional adult diagnostic algorithms are not directly applicable, and risk factors are often absent or atypical. Neonates requiring intensive care who have central venous catheters, sepsis, congenital anomalies, or prematurity are all at significantly heightened risk for venous thromboembolism (VTE), yet it must be acknowledged that reports of neonatal PE in the literature remain sparse.[2].\u003c/p\u003e\n\u003cp\u003eCTPA\u0026nbsp;remains the imaging standard for confirming PE in older children and adults, but it is well established that its real-world diagnostic yield is quite limited, with most studies reporting positive rates in the mid-teens percentage range. Moreover, CTPA is often impractical or unsafe in hemodynamically unstable neonates. Therefore, exclusive reliance on CTPA in critically ill infants can result in under-diagnosis while simultaneously subjecting low-probability cases to unnecessary ionizing radiation.[3].\u003c/p\u003e\n\u003cp\u003eBecause of the constraints outlined, bedside diagnostic strategies have a clearly defined and important role: transthoracic echocardiography is highly useful for detecting right ventricular (RV) dilation, dysfunction, or signs of pulmonary hypertension, and when combined with clinical risk stratification and laboratory markers such as markedly elevated D-dimer, it provides reliable evidence to support early empiric treatment in situations where definitive radiologic confirmation is not feasible. Contemporary pediatric VTE guidelines rightly emphasize individualized assessment and prompt initiation of anticoagulant or thrombolytic therapy for life-threatening thrombosis, while explicitly weighing the bleeding risks that are inherent to the neonatal period.[4].\u003c/p\u003e\n\u003cp\u003eThe article presents two cases of PE and uses them to very clearly illustrate the diagnostic difficulties inherent in evaluating hemodynamically unstable infants for PE when CTPA is not feasible, thus naturally leading to a discussion of the utility of combining bedside echocardiography with D-dimer assessment to establish a high pretest likelihood. More importantly, it emphasizes that prompt, guideline-informed intervention is life-saving in this rare but devastating condition. Therefore, the authors appropriately conclude by advocating for a high index of suspicion and the use of pragmatic, bedside-focused diagnostic pathways consistent with current pediatric VTE management principles for critically ill neonates. \u0026nbsp; \u0026nbsp;\u003c/p\u003e"},{"header":"Case presentation 1","content":"\u003cp\u003eA male infant was delivered vaginally by a G1P0 healthy mother after spontaneous onset of labor, and vaginal swab findings were negative for Streptococcus beta hemolytic, but positive for Ureaplasma urealyticum. There was no premature rupture of membranes, bloody amniotic fluid, or placental abruption during delivery. The pregnant woman has a complex medical history including threatened miscarriage, placental hypoplasia, pregnancy with hypokalemia, pregnancy with atopic dermatitis, thalassemia, hyperlipidemia, hypothyroidism, and polycystic ovary syndrome. The newborn experienced asphyxia after birth with a 1-minute Apgar score of 5 and a 5-minute Apgar score of 8.\u003c/p\u003e\u003cp\u003eAdmission physical examination showed widespread ecchymosis over the body, normal blood pressure and temperature, and a leukemia-like reaction following UU infection with white blood cell count 82.7*10^9/L, platelet count 253*10^9/L, and C-reactive protein\u0026thinsp;\u0026lt;\u0026thinsp;0.1. After resuscitation, arterial blood gas analysis yielded pH 7.02, PaCO2 103 mmHg, PaO2 85 mmHg, actual base excess 10.2 mmol/L, and lactate 4.7 mmol/L. Myocardial enzymes (CK-MB 158.0u/L) and electrolytes were all within normal limits, and the electrocardiogram showed normal sinus rhythm. Laboratory investigations confirmed normal platelet count and liver function tests. Echocardiography excluded congenital heart disease.\u003c/p\u003e\u003cp\u003eNon-invasive ventilator-assisted ventilation was started after admission, but at 12 hours of age the baby suddenly deteriorated with clear signs of cardiogenic shock (heart sounds absent, spontaneous breathing ceased), hence intubation and cardiopulmonary resuscitation were necessary. The resuscitation lasted approximately 10 minutes, after which no heart rate could be detected. Subsequent investigations revealed markedly elevated D-dimer levels (8880ug/L). From the chest X-ray there is no evidence of pneumothorax or decreased transparency, and all lung ultrasound exams show A-line patterns, whereas cardiac ultrasound demonstrates an enlarged right ventricle with preserved myocardial peristalsis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea) and dilation of pulmonary artery branches (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). Blood gas analysis confirms severe respiratory acidosis and metabolic acidosis, therefore acid correction treatment is indicated. No electrolyte abnormality was found, and white blood cell count is elevated while CRP is normal.\u003c/p\u003e\u003cp\u003eSince the patient was appropriately managed as a case of confirmed pulmonary embolism, and the clinical presentation was highly suggestive of pulmonary embolism, anticoagulant therapy with heparin was initiated immediately. CTPA could not be done because the disease was evolving too rapidly. After anticoagulation and cardiopulmonary resuscitation, the heart rate had returned to 90 beats per minute after 1 hour and 40 minutes, but oxygen saturation remained 65% lower. Right-to-left shunting was clearly seen in the ductus arteriosus, which confirmed the presence of pulmonary hypertension(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Following treatment with milrinone, the patient's condition improved steadily.\u003c/p\u003e\u003cp\u003eThe child had the same condition 83 hours after birth (platelet count 102*10^9/L, D-dimer levels 15670ug/L, cardiac ultrasound demonstrates an enlarged right ventricle), and because similar changes had recurred in the patient's course, a clear pattern emerged in the retrospective analysis: platelet count was decreasing while D-dimer was increasing. Given the insufficiency of anticoagulant strength at that time, thrombolytic therapy was given first, followed by anticoagulation therapy, but the symptoms did not recur. Therefore, the authors appropriately administered urokinase thrombolytic therapy on the basis of heparin anticoagulation, and as a result, the patient's platelets rebounded, D-dimer gradually returned to normal, and the same symptoms did not occur again.\u003c/p\u003e"},{"header":"Case presentation 2","content":"\u003cp\u003eA female infant, being the smaller of a pair of dizygotic twins, was delivered at 28 weeks' gestation by emergency caesarean section because of premature rupture of membranes, clinical chorioamnionitis, maternal urinary tract infection, and pre-gestational diabetes mellitus, with a birth weight of 1270 g. The Apgar scores at 1, 5, and 10 minutes after birth were 8, 9, and 9, respectively.\u003c/p\u003e\u003cp\u003eThe infant had widespread cutaneous bruising and markedly reduced breath sounds on physical examination, with the rest of the exam being unremarkable. Initial arterial blood gas analysis established a clear mixed respiratory and metabolic acidosis (pH 7.26, PaCO₂ 48.3 mmHg, PaO₂ 50 mmHg, base excess\u0026thinsp;\u0026minus;\u0026thinsp;5.8 mmol/L, lactate 0.8 mmol/L). Laboratory studies showed a white blood cell count of 7.5 \u0026times; 10⁹/L, hemoglobin 150 g/L, platelet count 143 \u0026times; 10⁹/L, and an elevated CRP level of 15.2 mg/L. The basic metabolic panel was otherwise normal except for hypoalbuminemia (26.2 g/L).\u003c/p\u003e\u003cp\u003eLung ultrasonography revealed an alveolar\u0026ndash;interstitial syndrome involving all lung fields bilaterally, and echocardiography confirmed a 1.5-mm patent ductus arteriosus (PDA) without any other evidence of structural congenital heart disease. Electrocardiography showed normal sinus rhythm. Because the infant developed progressive respiratory distress, endotracheal intubation and mechanical ventilation were performed, and an umbilical venous catheter was placed.\u003c/p\u003e\u003cp\u003eOn stnatal day 3 the infant had a sudden cardiorespiratory arrest, so immediate cardiopulmonary resuscitation was performed. Bedside lung ultrasound showed no pneumothorax, with predominant A-lines present, but cardiac and lung ultrasonography clearly demonstrated severe right ventricular pressure overload and dysfunction (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Laboratory studies confirmed a very high D-dimer level (3352 \u0026micro;g/L) and a low platelet count (30*10^9/L), whereas all electrolyte levels were normal.\u003c/p\u003e\u003cp\u003eBecause of the infant's history of birth trauma and umbilical venous catheterization, anticoagulation and thrombolytic therapy were appropriately initiated: an intravenous bolus of unfractionated heparin (50 U/kg) was given, followed by continuous alteplase infusion at 0.1 mg/kg/h and subsequent heparin maintenance therapy at 10 U/kg/h. At the same time, the patient's cardiac ultrasound showed pulmonary arterial hypertension (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb)and was given nitric oxide inhalation therapy. As a result of this well-organized multimodal approach, the infant's hemodynamic status stabilized quite nicely.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough neonatal PE has classically been considered rare, there is now ample evidence that its true incidence is severely underestimated in clinical practice[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The presenting symptoms of neonatal pulmonary embolism vary directly with the size of the thrombus, and most clinical manifestations are atypical, consisting of hypoxemia, hypercapnia, tachycardia, right heart failure, etc. Importantly, these symptoms are very commonly seen in other cardiovascular diseases, hence early diagnosis remains challenging.\u003c/p\u003e \u003cp\u003eSince the patients who experienced cardiac and respiratory arrest were excluded one by one according to the 6H5T principle, pulmonary embolism was considered the most likely diagnosis, and indeed the child had high-risk factors, markedly elevated D-dimer levels, and concurrent right heart dysfunction, all of which together very clearly established the diagnosis of pulmonary embolism. Therefore, prompt symptomatic treatment was initiated, and the children's conditions subsequently improved.\u003c/p\u003e \u003cp\u003eNeonatal PE almost always occurs in the setting of known comorbidities, systemic diseases, or other risk factors, hence it is fundamentally different from the description of idiopathic PE in the adult population[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In fact, 80% to 96% of children with pulmonary embolism have at least one identifiable risk factor[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], with the most commonly encountered ones being central venous catheters, sepsis, mechanical ventilation, perinatal asphyxia, congenital heart disease, dehydration, and birth trauma[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].Prematurity further magnifies this vulnerability, and maternal conditions such as infection, placental disease, diabetes, pre-eclampsia, antiphospholipid antibody syndrome and emergent Cesarean section have all been clearly and consistently associated with an increased risk of neonatal PE. Among the risk factors mentioned, central venous catheterization is increasingly associated with pulmonary embolism in children. These children not only have central venous catheters, but also high-risk factors such as perinatal asphyxia, low birth weight, premature birth, mechanical ventilation, infections, and autoimmune abnormalities and birth trauma. The neonatal and maternal factors listed\u0026mdash;perinatal asphyxia, low birth weight, premature birth, mechanical ventilation, infections, autoimmune abnormalities, and birth trauma\u0026mdash;collectively satisfy Virchow\u0026rsquo;s triad in critically ill neonates: venous stasis, endothelial injury, and a hypercoagulable state, therefore offering a clear and clinically relevant mechanistic framework for understanding the development of neonatal PE in this patient.\u003c/p\u003e \u003cp\u003eElevated D-dimer was a major biochemical clue supporting the diagnosis of pulmonary embolism in the neonate. In adults and older children, markedly increased D-dimer levels are well recognized as reliable indicators of active fibrin formation and degradation, and thus D-dimer testing with high sensitivity is routinely incorporated into diagnostic pathways for PE. Strouse et al. provided a clear and important analysis: markedly elevated D-dimer levels were present in nearly all children with imaging-confirmed VTE, but the test has limited specificity in the setting of infection or systemic inflammation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, although D-dimer alone cannot reliably differentiate VTE from other inflammatory diseases, patients with relevant risk factors will have a substantially increased detection rate of thrombosis, making immediate imaging examination and treatment consideration appropriate.\u003c/p\u003e \u003cp\u003ePE occurs rapidly and has a high mortality rate, but it must be noted that CTPA, although considered the gold standard for diagnosis, cannot be reliably used in newborns and critically ill children because of inherent risks such as high radiation exposure, invasiveness, contrast agent allergy, secondary arrhythmia, and bleeding [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, focused cardiac ultrasound protocols have been well validated in adults and older children as rapid, effective tools for assessing RV strain in suspected PE and guiding emergent management[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].The prevalence of right ventricular thrombus in patients with pulmonary embolism is known to be 4% to 18%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and echocardiography has a much higher positive rate for detecting pulmonary artery and right heart enlargement, decreased right ventricular ejection fraction, and tricuspid regurgitation. Therefore, in newborns, echocardiography plays an unparalleled diagnostic role, and its indirect signs are extremely useful and reliable evidence for acute pulmonary embolism in the setting of high-risk factors.\u003c/p\u003e \u003cp\u003eBecause hemodynamically unstable PE is best treated with rapid reperfusion using systemic thrombolysis, which promptly reduces right ventricular afterload and improves perfusion, this approach is generally regarded as first-line therapy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, applying this paradigm to preterm neonates presents major challenges, owing to the fact that most of the supporting evidence comes from case reports/series and extrapolations from older children and adults. There is currently no universally accepted consensus regarding alteplase dosing, escalation strategy, or infusion duration for premature infants with PE rather than catheter-related thrombosis, and preterm infants already have a higher baseline risk of intracranial hemorrhage, with thrombolysis itself increasing the major bleeding risk. Unfractionated heparin (UFH)is far more readily available in neonatal intensive care units, can be titrated rapidly, and has well-established reversal options, so clinicians may reasonably initiate UFH promptly and then consider \u0026ldquo;rescue\u0026rdquo; thrombolysis on top of anticoagulation if there is persistent cardiovascular collapse or progressive right heart failure.\u003c/p\u003e \u003cp\u003eThese cases also contribute to the evolving understanding that PE should be considered early in any neonate with unexplained recurrent apnea, sudden bradycardia, or cardiopulmonary arrest, especially when risk factors coexist. Traditional reliance on CTPA in this population is clearly inadequate, so a multi-modal diagnostic paradigm that integrates clinical triggers, laboratory markers, point-of-care echocardiography, and individualized risk assessment is likely to offer greater sensitivity and better safety. More importantly, the case itself demonstrates that early bedside evaluation with prompt anticoagulant therapy substantially reduces morbidity and mortality in neonatal thrombotic events.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePE Pulmonary embolism\u003c/p\u003e \u003cp\u003eCTPA computed tomography pulmonary angiography\u003c/p\u003e \u003cp\u003eUFH Unfractionated heparin\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhen Zhao drafted the manuscript. Xiaoxia Li and Jing Li polished the language and\u003c/p\u003e\n\u003cp\u003eadjusted the format. Shujun Hong revised the manuscript. Lili Xu and Zhiqun Zhang revised the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable. All authors consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and/or clinical images was obtained from the parents of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCowan AD et al. A case report of an unprovoked neonatal pulmonary embolism:management strategies and cardiopulmonary complications.European heart journal.Case reports, 2024.8(11):p.ytae527-ytae527.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuzman RE, et al. Thromb Neonatal Intensive Care Unit NeoReviews. 2023;24(6):pe356\u0026ndash;e369.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Boer HC, et al. 10, 589 CT pulmonary angiograms:evaluating the yield of acute pulmonary embolism. Br J Radiol. 2022;95(1137):p20220254\u0026ndash;20220254.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaidi AU, Hutchins KK. M Rajpurkar Pulmonary Embolism Child Front Pediatr. 2017;5:p170\u0026ndash;170.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanerkin NG. Pulmonary thrombo-embolic phenomena in the newborn. J Pathol Bacteriol. 1966;91(2):p569\u0026ndash;574.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnopoff K, et al. Thromb Disorders Newborn NeoReviews. 2024;25(11):pe710\u0026ndash;e719.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaggio A et al. Pulmonary embolism in children, a real challenge for the pediatrician:a case report and review of the literature.Acta bio-medica:Atenei Parmensis, 2022.93(S3):\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003epp. e2022055-e2022055\u003c/span\u003e\u003cspan address=\"http://pp. e2022055-e2022055\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClement R et al. Cerebellar-pulmonary embolism, cause of death in the newborn.Journal of clinical forensic medicine, 2006.13(6\u0026ndash;8):pp. 361\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrouse JJ, et al. D-dimer for the diagnosis of venous thromboembolism in children. Am J Hematol. 2009;84(1):p62\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThacker PG, Lee EY. Advances in Multidetector CT Diagnosis of Pediatric Pulmonary Thromboembolism. Korean J Radiol. 2016;17(2):p198\u0026ndash;208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRecker F, et al. Applications of Point-of-Care-Ultrasound in Neonatology:A Systematic Review of the Literature.Life(Basel. Switzerland). 2024;14(6):p658.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrada G, Stainback RF, D\u0026iacute;az-G\u0026oacute;mez JL. Focused Cardiac Ultrasonography for Right Ventricular Size and Systolic Function.Reply.The New England journal of medicine, 2023.388(12):pp1150\u0026ndash;1151.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMay\u0026agrave;-Casalprim G et al. Floating right heart thrombus causing pulmonary embolism in a patient with acute ischaemic stroke:A case report and review of literature.Neurologia, 2020.35(9):pp661\u0026ndash;663.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRouleau SG, et al. Management of high-risk pulmonary embolism in the emergency department:A narrative review. Am J Emerg Med. 2024;79:1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary embolism, Neonate, Echocardiography, D-dimer levels, Case report","lastPublishedDoi":"10.21203/rs.3.rs-9126844/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9126844/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePulmonary embolism (PE) is traditionally regarded as extremely rare in neonates, but there is now strong evidence that its true incidence is seriously underestimated because of nonspecific clinical manifestations and the limited utility of standard diagnostic pathways in this population. In hemodynamically unstable infants, computed tomography pulmonary angiography (CTPA), the diagnostic gold standard in adults, is often impractical, hence the urgent need for alternative bedside-focused diagnostic strategies.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eWe describe two 28-week premature neonates who had episodes of cardiopulmonary arrest and who underwent thorough investigation, yielding no evidence of structural cardiac abnormalities, pneumothorax, electrolyte disturbance, or infectious complications. Bedside studies disclosed markedly elevated D-dimer levels and transthoracic echocardiographic findings of right ventricular dilation, impaired systolic function, and indirect signs of pulmonary hypertension. Because neonatal pulmonary embolism is rapid and dangerous and the infeasibility of CTPA in the unstable clinical context, empiric anticoagulation with heparin was initiated, followed by thrombolytic therapy due to persistent clinical deterioration. The patient had rapid hemodynamic recovery and normalization of D-dimer levels.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe cases make it very clear that a high index of suspicion for PE should be maintained in neonates with unexplained hemodynamic collapse, recurrent apnea, or cardiorespiratory arrest, especially when risk factors are present. Therefore, a multi-modal diagnostic approach combining clinical evaluation, D-dimer testing, and focused echocardiography is optimal when CTPA is not feasible. Prompt, guideline-directed anticoagulant and thrombolytic strategies can markedly improve outcomes in this rare but devastating condition.\u003c/p\u003e","manuscriptTitle":"Two case reports of neonatal pulmonary embolism with respiratory and cardiac arrest as the first symptom","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-03 11:18:35","doi":"10.21203/rs.3.rs-9126844/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"45262834163928134133884774811122501038","date":"2026-04-05T17:00:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299747593450181914550010142715054811215","date":"2026-04-03T13:35:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-31T18:37:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301980538169212081893978497272244565896","date":"2026-03-31T18:14:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-30T17:57:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"165398753091246672667162904650783103919","date":"2026-03-30T17:30:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-28T16:41:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-18T06:29:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-18T00:56:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-18T00:56:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-03-15T07:11:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e319a90c-ebe3-4259-85a4-3f5495b62dcd","owner":[],"postedDate":"April 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-03T11:18:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-03 11:18:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9126844","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9126844","identity":"rs-9126844","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}